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Methods of treating neurodegenerative disorders

a neurodegenerative disorder and treatment method technology, applied in the direction of biocide, drug composition, genetically modified cells, etc., can solve the problems of poor clinical outcome, no effective treatment, and associated apoe4

Inactive Publication Date: 2009-05-28
THE J DAVID GLADSTONE INST A TESTAMENTARY TRUST ESTABLISHED UNDER THE WILL OF J DAVID GLADS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0006]The present invention provides a selected population of neural cells, including neural stem cells, neural progenitor cells, neural precursor cells, and progeny thereof, which neural cells are selected for one or both of an apoE4− phenotype and an apoE3+ phenotype. The selected population of ne

Problems solved by technology

ApoE4 is also associated with poor clinical outcome and with earlier onset, progression, or severity of head trauma, stroke, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis.
There are a number of neurodegenerative disorders for which there is currently no effective treatment.

Method used

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Examples

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example 2

[0087]Tissue from a particular neural region is removed from the brain using a sterile procedure, and the cells are dissociated using any method known in the art including treatment with enzymes such as trypsin, collagenase and the like, or by using physical methods of dissociation such as with a blunt instrument. Dissociation of fetal cells can be carried out in tissue culture medium. An exemplary medium for dissociation of juvenile and adult cells is low Ca2+ artificial cerebral spinal fluid (aCSF). Regular aCSF contains 124 mM NaCl, 5 mM KCl, 1.3 mM MgCl2, 2 mM CaCl2, 26 mM NaHCO3, and 10 mM D-glucose. Low Ca2+ aCSF contains the same ingredients except for MgCl2 at a concentration of 3.2 mM and CaCl2 at a concentration of 0.1 mM. Dissociated cells are centrifuged at low speed, between 200 and 2000 rpm, e.g., between 400 and 800 rpm, and then resuspended in culture medium. The neural cells can be cultured in suspension or on a fixed substrate. In some embodiments, the neural cells...

example 3

[0088]Dissociated neural cells are placed into any known culture medium capable of supporting cell growth, including HEM, DMEM, RPMI, F-12, and the like, containing supplements which are required for cellular metabolism such as glutamine and other amino acids, vitamins, minerals and useful proteins such as transferrin and the like. Medium may also contain antibiotics to prevent contamination with yeast, bacteria and fungi such as penicillin, streptomycin, gentamicin and the like. In some embodiments, a defined, serum-free culture medium is used. An exemplary culture medium is a defined culture medium comprising a mixture of DMEM, F12, and a defined hormone and salt mixture. Another exemplary defined culture medium is a defined culture medium as described in WO 95 / 00632.

example 4

[0089]Another suitable culture medium comprises cell viability and cell proliferation effective amounts of the following components: (a) a standard culture medium being serum-free (containing 0-0.49% serum) or serum-depleted (containing 0.5-5.0% serum), known as a “defined” culture medium, such as Iscove's modified Dulbecco's medium (“IMDM”), RPMI, DMEM, Fischer's, alpha medium, Leibovitz's, L-15, NCTC, F-10, F-12, MEM and McCoy's; (b) a suitable carbohydrate source, such as glucose; (c) a buffer such as MOPS, HEPES or Tris, e.g., HEPES; (d) a source of hormones including insulin, transferrin, progesterone, selenium, and putrescine; (e) one or more growth factors that stimulate proliferation of neural stem cells, such as EGF, bFGF, PDGF, NGF, and analogs, derivatives and / or combinations thereof, e.g., EGF and bFGF in combination; (f) LIF.

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Abstract

The present invention provides a selected population of neural cells, including neural stem cells, neural progenitor cells, neural precursor cells, and progeny thereof, which neural cells are selected for an apoE4− phenotype. In some embodiments, the neural cells are further selected for an apoE3+ phenotype. The selected population of neural cells is useful in treating various disorders, such as neurodegenerative disorders and demyelination diseases. The present invention further provides methods of treating neurodegenerative disorders and demyelinating diseases, generally involving administering a subject selected cell population.

Description

CROSS-REFERENCE[0001]This application claims the benefit of U.S. Provisional Patent Application No. 60 / 876,944, filed Dec. 22, 2006, which application is incorporated herein by reference in its entirety.BACKGROUND[0002]Apolipoprotein E (apoE), a 34,000 molecular weight protein, is the product of a single gene on chromosome 19 and exists in three major isoforms designated apoE2, apoE3 and apoE4. ApoE mRNA is abundant in the brain, where it is synthesized and secreted primarily by astrocytes. Although apoE is synthesized in the brain primarily by astrocytes, neurons in the central nervous system (CNS) express apoE in response to excitotoxic stress and other insults.[0003]It has been shown that neuronal expression of apoE, especially apoE4, contributes to the pathogenesis of Alzheimer's Disease (AD), such as neurofibrillary tangle formation and mitochondrial dysfunction. ApoE4 is a major risk factor for AD. AD patients with apoE4 have greater hippocampal atrophy than those without apoE...

Claims

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Application Information

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IPC IPC(8): A61K35/12C12N5/00A61P25/28
CPCA61K35/12C12N2510/00C12N2501/115C12N5/0623A61P25/28
Inventor HUANG, YADONGLI, GANGMAHLEY, ROBERT W.XU, QIN
Owner THE J DAVID GLADSTONE INST A TESTAMENTARY TRUST ESTABLISHED UNDER THE WILL OF J DAVID GLADS
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